The invention relates to a device for cooling, in particular freezing, goods to be cooled, in particular biological materials.
Devices for freezing biological materials are known from cryobiology.
In many fields of biological specimen preparation as well as intense-cooling conservation or vitrification of cells, organs or organisms or other biological materials, for various reasons it is crucial to cool specimens as fast as possible.
In the case of biological specimen preparation by cryotechniques e.g. for histology examinations, it is important that the specimen morphology be maintained as far as possible in spite of cooling the specimen. This requires rapid cooling to keep the extent of ice formation to a minimum.
Devices for freezing blood cells are particularly well researched. With these devices, antifreeze additives such as for example hydroxyethyl starch (HES) or glycerine is added to the blood components; said additives are necessary to achieve an adequate cell survival rate after the freeze-thaw process. The blood components present in a film bag are placed in a container which is subsequently cooled by immersion in e.g. liquid nitrogen.
To achieve a good ratio of surface to volume at the bag and to avoid creases and bulges at the bag, DE 31 42 521 C2 and DE-A-44 37 091 propose that the bag be held between two plates arranged parallel in respect of each other, and that the bag be cooled in the liquid nitrogen together with the holding device. A similar holding device is also known from WO 90/09184.
From U.S. Pat. No. 4,018,911 a holding device is known where the bags are positioned loosely in a perforated holding device so that the coolant can reach the bags also through the holding device.
However, the known holding devices have a disadvantage in that thermal transmission from the coolant to the biological material is impeded by the holding device.
It is thus the object of the invention to provide a device of the generic type which allows acceleration of the cooling process of goods to be cooled.
The object of the invention is met by a generic device comprising a holding device which during the cooling process holds the goods to be cooled essentially in a non-deformable way and forms at least one space which allows direct contact between the coolant and the goods to be cooled, with channels for conducting the coolant being provided between the holding device and the goods to be cooled.
Preferably, the space extends at least partly along the goods to be cooled.
In the case of boiling coolants, the guide channels for conducting the coolant allow free convection or pumping of the coolant through the channels.
The holding device according to the invention is constructed such that it holds in particular liquid blood components filled into bags in a shape that is advantageous for cooling while nevertheless allowing direct contact between the coolant and the goods to be cooled. This not only results in optimum holding of the goods to be cooled but also in avoiding the problems, known from the state of the art, of thermal transmission from the goods to be cooled through the holding device into the coolant.
To achieve good thermal transmission from the goods to be cooled to the coolant, it is proposed that the contact surface between the holding device and the goods to be cooled be smaller than the contact surface between the coolant and the goods to be cooled.
Trials have shown that convection through evaporation itself, within the described guide channels, results in strong acceleration of the coolant if the inlet of the guide channels is arranged lower than their outlet.
This chimney effect is so pronounced that it is proposed that flow-control devices which are adjustable so as to restrict the flow, be arranged at the inlet and/or the outlet. This makes it possible to achieve control or regulation of the coolant flow in a simple way. It is advantageous if the adjustable flow-control devices are adjustable also during the cooling process, so that variations in the cooling rates between the margin and the middle of the specimen can be compensated for by regulation, because otherwise different local survival rates could result.
Simple construction of the device is achieved in that the holding device holds the goods to be cooled in the form of a plate. In particular good cooling rates can be achieved by cooling both sides of the plate-shaped goods to be cooled.
The goods to be cooled can however also be held in the form of a cylinder. Particularly advantageous is a holding device which holds the goods to be cooled in the form of a hollow cylinder because in this way the goods to be cooled encompass a hollow space which can serve as a guide channel for the coolant.
Since in the range of the boiling temperature of the coolant the best cooling rate can be achieved with nucleate boiling, a chamber is proposed into which the holding device can be inserted, with said chamber preferably being heatable. The ability to heat the chamber allows precise setting of the evaporation rate of the coolant and thus of the convection. Alternatively or additionally, the holding device itself can be constructed so as to be heatable.
It is advantageous if the chamber comprises an inlet with a coolant pump. In this way forced flow of the coolant through the chamber and between the goods to be cooled and the holding device can be achieved, with said forced flow improving the thermal transmission from the goods to be cooled to the coolant.
A preferred embodiment provides for the chamber to comprise an overflow and a separator for liquid coolant. While the liquid coolant is used for further cooling, the gaseous part of the coolant is either discarded or liquefied in a connected device.
A preferred use of the device described comprises the freezing of bags filled with a liquid, in particular blood components. These bags are flexible in shape; they have to be cooled as fast as possible. Although antifreeze additives limit the damage to blood components, particularly high rates of cooling should be achieved. This can be achieved in a simple way with the device described.
When cooling bodies and in particular when cooling liquids, the volume of the goods to be cooled changes, in the case of aqueous systems in addition also due to crystallisation.
It is thus proposed that the holding device described essentially be pressed against the goods to be cooled, at a constant pressure. This can for example be achieved by a pre-tensioned spring with flat spring characteristics, with pneumatic or hydraulic devices. In particular, a hydraulic or pneumatic device with respective control makes it possible to keep the pressure against the goods to be cooled essentially constant. Although the volume increase during crystallisation can principally be absorbed by regulating the pressure, it is additionally advantageous if the film bag is not completely filled, but instead, if a gas cushion is left above the goods to be frozen. In this way the welded seams of the bag are not unduly stressed by the expansion in volume.
In order to improve the thermal transmission at the holding device, it is proposed that the holding device comprise a microporous surface on the side of the coolant. To form a microporous surface, either the surface itself can be roughened or an adhesive layer with a microporous surface, for example Leukosilk(copyright) can be applied to the surface. It is particularly advantageous if this microporous layer is fixed directly to the bag.
Depending on the device selected, or depending on the desired cooling progression, prior to cooling the goods to be cooled, the temperature of the holding device can be below the solidification temperature of the goods to be cooled. But it is also possible that the temperature of the holding device is above the solidification temperature of the goods to be cooled.